Arrhythmic events in clustered human pluripotent stem cell-derived cardiomyocytes

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Authors

PEŠL Martin PŘIBYL Jan KLIMOVIČ Šimon ŠČUREK Martin BECKEROVÁ Deborah STÁREK Zdeněk BRAT Kristián ROTREKL Vladimír

Year of publication 2021
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

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Description Aminophylline is a methylxanthine bronchodilator with a documented proarrhythmic action. We aimed to describe changes in rhythm pattern of spontaneously beating human pluripotent stem cell-derived cardiomyocytes (hPSC-CM). Moreover the inotropic changes were never before studied in hPSC-CM. Methods: hPSC-CM were differentiated in clusters[1-3] basic biomechanical parameters, such as the average value of contraction force and the beat rate (BR), were assessed by atomic force microscopy (AFM) as previously described[1,2]. Cells were stabilized in Tyrode solution (baseline) and applied were increasing concentrations of aminophylline (10 µM, 100 µM, 1 mM, and 10 mM). Results: the 10mM aminophylline significantly increased beat rate (BR) in comparison with the lower concentrations. There were no significant differences in inotropic effects of aminophylline on the hPSC-CMs between all groups and concentrations. Number of measured clusters underwent atypical arrhythmic pattern - termed "stop&go effect" - presenting as a series of fast BR episodes (the equivalent of tachycardia) followed by inactivity. This effect occurred during aminophylline treatment with various concentrations. Conclusions: an aberrant cardiomyocyte response to aminophylline was observed, suggesting an arrhythmogenic potential of the drug. Our data represent a missing link between the arrhythmic events related to the aminophylline/theophylline treatment in clinical practice and subcellular mechanisms of methylxanthine arrhythmogenesis. AFM combined with hPSC-CM serve as a robust platform for direct drug effects screening.
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